Changes to environment variables should take effect immediately, if you make the change via the main Properties dialog for the computer in question (go to My Computer | Properties | Advanced | Environment Variables). After the changes are saved, Explorer broadcasts a WM_SETTINGCHANGE
message to all windows to inform them of the change. Any programs spawned via Explorer after this should get the updated environment, although already-running programs will not, unless they handle the setting change message.
I’m not able to tell from your problem description what specific problem you’re having with this. Can you tell us more about the specific scenario that isn’t working?
This KB article may also be of use: How to propagate environment variables to the system
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